Study of Cholic Acid Conjugation by Isolated Rat Hepatocytes

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Abstract
The ability of isolated rat hepatocytes to conjugate cholic acid was studied to discover the role of conjugation in the regulation of hepatic transport of unconjugated bile acids. Determination of intracellular bile acids showed that cholic acid was conjugated primarily with taurine and glycine, with taurine representing 70-80% of the total. The conjugating capacity was comparable to that of rat liver in vivo and could be increased by taurine and glycine. The uptake rate of cholic acid could not be influenced by increasing the conjugation rate and taurine and glycine. Conjugation did not affect the steady-state distribution of total bile acids between the medium and the cells. The individual bile acid concentrations did not reach a steady-state level during the incubation period of 1 h and could be influenced by increasing conjugation. The conjugation pattern was altered by taurine and glycine. The conjugating ability of the isolated rat hepatocytes may be comparable to that of the rat liver in vivo. Transport of unconjugated bile acids may not be regulated by conjugation. Total bile acid, instead of individual bile acids, may be maintained at steady state by the hepatocytes. The same enzyme may catalyze the conjugation of bile acid-CoA with taurine and glycine. Isolated rat hepatocytes should provide a suitable model for the study of drug-induced changes in bile acid conjugation at the cellular level.